Scientists say they have pinpointed a protein which they believe may play a pivotal role in depression.
Depression is linked to the chemical serotonin
A team from Rockefeller University in New York found mice deficient in the protein - p11 - showed signs of depression-like behaviour.
In contrast, raising levels was shown to have an anti-depressant effect on the animals.
Writing in the journal Science, they say p11 appears to help regulate a brain chemical linked to mood.
However, a UK expert said the biochemical regulation of depression was likely to be complex.
The chemical, serotonin, is a key target of anti-depressants, and has been implicated not only in depression, but also in anxiety disorders.
Brain cells use serotonin, and other chemicals, to communicate with each other.
The chemicals bind to receptors on the surface of the receiving cells. However, exactly how these receptors work remains a mystery.
Drawn to surface
The Rockefeller team found that p11 seems to play a role in drawing one particular type of serotonin receptor to the surface of cells.
This suggested that a lack of p11 might result in a deficiency of receptors - and thus increase the likelihood of depression.
The researchers examined the brains of depressed people and mice showing signs of depressed behaviour - and found p11 levels were substantially lower in both.
Next, they showed that treating mice with two types of anti-depressants and electroconvulsive therapy (ECT) all boosted p11 levels in the animals' brains.
Lead researcher Dr Paul Greengard said: "They all work in totally different ways, but in all cases they caused the same biochemical change.
"So, it's pretty convincing that p11 is associated with the main therapeutic action of anti-depressant drugs."
The researchers were able to trigger symptoms of depression in mice by lowering their p11 levels, and produce the opposite effect by raising levels of the protein.
Further analysis showed that this seemed to be related to the number and responsiveness of serotonin receptors on the surface of the animals' brain cells.
Professor David Nutt, head of psychopharmacology at Bristol University, told the BBC News website the research held out hope of new drugs which would work in different ways to those currently available for depression.
He said currently drugs helped about 60% of people to get well, had some effect on another 20%, but were of little help for the remaining 20%.
The hope would be that a new drug would boost success rates and "improve the efficacy of those that we already have," he said.
Professor Dave Kendall, of the University of Nottingham, said the research was interesting, but questioned whether depression was likely to be controlled by just one protein.
He said: "There are a number of proteins that increase in various parts of the brain following anti-depressant treatments of various sorts."
Professor Kendall said drugs that directly activated the receptor studied by the Rockefeller team had been shown to increase, not decrease anxiety in studies on animals.
"Maybe p11 has other functions in addition to controlling receptor expression that are important in depression," he said.